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CD3
Hindawi Publishing Corporation
Journal of Immunology Research
Volume 2016
+ + ? CD3 CD8 CD28 T Lymphocytes in Patients with Lupus Nephritis
Marcelina gabiNska 0
Magdalena Krajewska 0
Katarzyna KoVcielska-Kasprzak 0
Marian Klinger 0
Oscar Bottasso
0 Department and Clinic of Nephrology and Transplantation Medicine, Faculty of Postgraduate Medical Training, Wroclaw Medical University , Borowska 213, 50-556 Wroclaw , Poland
The results of studies on the CD3+CD8+CD28? cells in SLE are inconsistent since several analyses describe CD3+CD8+CD28? as either immunosuppressive or cytotoxic. The aim of this study is to inquire whether the quantitative changes of CD3+CD8+CD28T lymphocytes subpopulation are related to the clinical status of patients with lupus nephritis. Evaluation of Foxp3 expression on CD3+CD8+CD28? cells may shed some light on functional properties of these cells. 54 adult SLE patients and 19 sex and age matched healthy volunteers were enrolled in the study. There were 15 patients in inactive (SLEDAI ? 5) and 39 in active (SLEDAI > 5) phase of disease. We determined absolute count of CD3+CD8+CD28? and CD3+CD8+CD28?Foxp3+ subpopulations by flow cytometry. We observed a statistically significant increase in absolute count and percentage of CD3+CD8+CD28? in SLE patients compared to HC ( < 0.001 ). Moreover there was significant positive correlation between increasing absolute count of CD3+CD8+CD28? cells and disease activity measured by SLEDAI ( s = 0.281, = 0.038 ). Active LN patients had increased absolute count of CD3+CD8+CD28cells compared to HC. Positive correlation of CD3+CD8+CD28? number with disease activity, and lack of Foxp3 expression on these cells, suggests that CD3+CD8+CD28? lymphocytes might be responsible for an increased proinflammatory response in the exacerbation of SLE.
1. Introduction
T CD8+ cells play a key role in the recognition and removal
of cells infected by intracellular pathogens [
1
] and also in
antitumor response [
2
]. Binding of T CD8+ surface receptor
TCR and MHC-I-bound antigen, found on the professional
antigen presenting cell?s (pAPC) surface, leads to T CD8+
activation [
3
]. Since stimulation only through the TCR
receptor is unable to maintain optimum T CD8+
activation, the second costimulatory signal is essential for full
activation and survival of these cells [
4
]. The best known
costimulatory signal is provided by the interaction of CD28
molecules presented on the T lymphocyte as well as the CD86
and CD80 molecules expressed on the pAPC?s surface [
3
].
Adequate signal power delivered to naive T CD8+ results
in the proliferation and differentiation of two cell types.
One of these is cytotoxic T lymphocytes (CTL), which
after reaching maturity and fulfilling their effector function
undergo apoptosis. The second type is T CD8+ memory cells,
both central and effector. Their continuous presence in the
circulation is essential to control another potential exposure
to the same antigen in a faster and more ef fective way [
5
].
Under chronic antigen stimulation, repeated cycles of
activation occur and lead to progressive and irreversible
reduction in CD28 molecule expression on the lymphocyte
surface. This results in accumulation of ?highly
antigenexperienced? T-cell with CD8+CD28? phenotype
characterized by extremely shortened telomeres [
6
].
There is a close relationship between CD28 molecules
presence and degeneration of the telomeres/telomerase.
Telomerase activity is necessary for cell proliferation,
cytokines and chemokines production, and antiviral activity.
However, lack of CD28 molecules leads to loss of ability to
increase telomerase activity in activated cells. Maintaining
the presence of CD28 molecule through gene transduction
in vitro slows down the ?immune aging? and improves the
efficiency of the immune system [
7
]. Telomeres are set up on
chromosomes ends and ensure their stability. Unprotected
chromosomes ends are exposed to a high risk of degradation.
Such degradation processes lead to the genetic information
loss and cell death [
8
]. This process functions as a mitotic
clock, while telomere length represents the number of cell
divisions [
9
].
Relationship has been demonstrated between the average
telomere length in peripheral blood cells and autoimmune
diseases, such as SLE [
10, 11
], rheumatoid arthritis [12],
systemic sclerosis (SSc) [
13
], ANCA-associated vasculitis
(AAV) [
14
], psoriasis, and atopic dermatitis [
15
].
It is now believed that one of the major causes of abnormal
immune response is the telomere properties dysfunction that
leads to autoimmunity [
16
]. Nonetheless some authors did
not confirm the relationship between telomere dysfunction
and the development of SLE [
17
]. It has been also observed
that the loss of CD28 is associated with increased surface
expression of the CD57 molecule. T CD8+CD28? cells
(CD8+CD57+) are referred to as antigen-specific, terminally
differentiated, but al (...truncated)